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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

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neo_2021_210127N141

Title: Differential expression of novel immune checkpoint receptors on tumor-infiltrating lymphocytes in patients with locally advanced breast cancer after neoadjuvant chemotherapy
Author: Aykhan Abbasov, Esin Aktas Cetin, Neslihan Cabioglu, Baran Mollavelioglu, Semen Onder, Selman Emiroglu, Mustafa Tükenmez, Mahmut Muslumanoglu, Abdullah Igci, Gunnur Deniz, Vahit Ozmen

Abstract: Immune checkpoint receptors (ICRs) were recently found to modulate the anti-tumoral immune response. This study aimed to determine the clinical and pathological associations of ICRs expression on tumor-infiltrating lymphocytes (TILs) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC).
Expressions of ICRs including PD-1, LAG-3, TIM-3, TIGIT, and CTLA-4 on CD8+ T lymphocytes and Natural Killer (NK) cells on TILs were analyzed by flow cytometry. Patients o have increased LAG-3 expression on CD16-CD56bright NK cells (p = 0.042) and PD-1 (p = 0.014) and CTLA-4 (p = 0.018) expressions on CD8+ T cells in regard to those with ypT1-T2, respectively. Contrarily, PD-1 expression on CD16-CD56bright NK cells was found to be decreased in patients with ypN+ compared to those with ypN- (p = 0.022). Furthermore, patients with HER2+ tumors were more likely to have increased TIM-3 expression on CD8+ T cells (p = 0.043), whereas patients with a better response to NAC were more likely to express TIGIT on CD8+ T (p = 0.014) and CD16- CD56bright NK cells (p = 0.003), respectively. The new generation ICRs, TIM-3, LAG-3, and TIGIT are highly expressed in LABC following NAC in patients with poor prognostic factors. Therefore, new evolving therapies using inhibitory mAbs directed to TIM-3, LAG-3, and TIGIT could be also be considered in locally advanced breast cancers expressing these ICRs.

Keywords: locally advanced breast cancer; PD-1; TIGIT; CTLA-4, LAG-3, TIM-3
Published online: 07-Jun-2021
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2021_210127N141


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